Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26992 | 81199;81200;81201 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| N2AB | 25351 | 76276;76277;76278 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| N2A | 24424 | 73495;73496;73497 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| N2B | 17927 | 54004;54005;54006 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| Novex-1 | 18052 | 54379;54380;54381 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| Novex-2 | 18119 | 54580;54581;54582 | chr2:178565158;178565157;178565156 | chr2:179429885;179429884;179429883 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs754446799  |
None | 0.81 | N | 0.605 | 0.078 | 0.268660756437 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/M | rs754446799 |
None | 0.81 | N | 0.605 | 0.078 | 0.268660756437 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47037E-05 | 0 | 0 |
| I/T | rs771535559 |
-2.101 | 0.549 | N | 0.651 | 0.39 | 0.600314364428 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/T | rs771535559 |
-2.101 | 0.549 | N | 0.651 | 0.39 | 0.600314364428 | gnomAD-4.0.0 | 2.05323E-06 | None | None | None | None | N | None | 5.98193E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9964E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7636 | likely_pathogenic | 0.7087 | pathogenic | -2.528 | Highly Destabilizing | 0.25 | N | 0.639 | neutral | None | None | None | None | N |
| I/C | 0.804 | likely_pathogenic | 0.7635 | pathogenic | -1.461 | Destabilizing | 0.977 | D | 0.759 | deleterious | None | None | None | None | N |
| I/D | 0.9977 | likely_pathogenic | 0.9972 | pathogenic | -3.069 | Highly Destabilizing | 0.972 | D | 0.827 | deleterious | None | None | None | None | N |
| I/E | 0.9949 | likely_pathogenic | 0.9938 | pathogenic | -2.728 | Highly Destabilizing | 0.92 | D | 0.795 | deleterious | None | None | None | None | N |
| I/F | 0.2652 | likely_benign | 0.2393 | benign | -1.524 | Destabilizing | 0.002 | N | 0.331 | neutral | None | None | None | None | N |
| I/G | 0.9734 | likely_pathogenic | 0.9643 | pathogenic | -3.142 | Highly Destabilizing | 0.92 | D | 0.788 | deleterious | None | None | None | None | N |
| I/H | 0.9892 | likely_pathogenic | 0.9849 | pathogenic | -3.041 | Highly Destabilizing | 0.992 | D | 0.848 | deleterious | None | None | None | None | N |
| I/K | 0.9914 | likely_pathogenic | 0.9897 | pathogenic | -1.756 | Destabilizing | 0.896 | D | 0.799 | deleterious | N | 0.502995392 | None | None | N |
| I/L | 0.0732 | likely_benign | 0.0713 | benign | -0.663 | Destabilizing | 0.001 | N | 0.205 | neutral | N | 0.345824486 | None | None | N |
| I/M | 0.1131 | likely_benign | 0.1073 | benign | -0.859 | Destabilizing | 0.81 | D | 0.605 | neutral | N | 0.482502146 | None | None | N |
| I/N | 0.9729 | likely_pathogenic | 0.9668 | pathogenic | -2.554 | Highly Destabilizing | 0.972 | D | 0.833 | deleterious | None | None | None | None | N |
| I/P | 0.9945 | likely_pathogenic | 0.9917 | pathogenic | -1.279 | Destabilizing | 0.972 | D | 0.833 | deleterious | None | None | None | None | N |
| I/Q | 0.9858 | likely_pathogenic | 0.9813 | pathogenic | -2.092 | Highly Destabilizing | 0.972 | D | 0.841 | deleterious | None | None | None | None | N |
| I/R | 0.9858 | likely_pathogenic | 0.9828 | pathogenic | -2.087 | Highly Destabilizing | 0.896 | D | 0.834 | deleterious | N | 0.502995392 | None | None | N |
| I/S | 0.9311 | likely_pathogenic | 0.912 | pathogenic | -3.007 | Highly Destabilizing | 0.617 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/T | 0.8556 | likely_pathogenic | 0.8196 | pathogenic | -2.491 | Highly Destabilizing | 0.549 | D | 0.651 | neutral | N | 0.484637648 | None | None | N |
| I/V | 0.1058 | likely_benign | 0.0862 | benign | -1.279 | Destabilizing | 0.002 | N | 0.232 | neutral | N | 0.466852329 | None | None | N |
| I/W | 0.981 | likely_pathogenic | 0.9726 | pathogenic | -1.846 | Destabilizing | 0.992 | D | 0.844 | deleterious | None | None | None | None | N |
| I/Y | 0.9169 | likely_pathogenic | 0.8942 | pathogenic | -1.685 | Destabilizing | 0.447 | N | 0.689 | prob.neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.